Cervical cancer has become the second leading cause of death of cancers, causing 250,000 deaths worldwide annually. Cervical cancer has been known to be mostly caused by a human papilloma virus (HPV) infection (zur Hausen, H et al. Biochem Biophys Acta 1996, 1288; F55-F78). Among hundreds of types of HPVs, HPV16 is known as the leading cause of cervical cancer (Mark H et al. J Natl Cancer Inst 1993, 85; 958-964). Among the HPV proteins, E6 and E7 proteins play critical roles in the occurrence of cervical cancer as oncogenes, and it has been reported that they are the major proteins which are expressed in about 99% of the tumors caused by HPVs. As a result, E6 and E7 proteins have become a major target antigen in the preparation of a vaccine to treat and prevent the cervical cancer (von Knebel Doeberitz et al. Int. J. Cancer 1992, 51; 831-834). E6 prevents apoptosis of the cells by inducing decomposition of a tumor-inhibiting protein p53, and E7 binds to a retinoblastoma protein (Rb) which is a cellular tumor suppressor, to inactivate the protein, and then to induce the cells to enter an S phase in the cell cycle (Cobrinik et al., Trends Biochem Sci 1992, 17:312-5).
A clinical test using a composition expressing a nucleic acid base sequence which expresses HPV16 E6 and E7 proteins at the same time was performed in order to treat the cervical cancer, but its therapeutic effect was not significant (Garcia F et al. Obstet Gynecol 2004, 103; 317-326). Further, International Patent Publication WO 2004/030636 discloses a fusion polypeptide comprising E6 and E7, wherein the E6 is at an amino terminal or a carboxyl terminal, and a polynucleotide encoding the fusion polypeptide. However, the polypeptide as disclosed in this document still has limitation in treating the cervical cancer caused by HPV.
Therefore, the present inventors have found that a fusion protein comprising an E6/E7 fusion polypeptide of HPV bonded with a secretory peptide and an immune enhancing peptide improves immune responses, and is effective in treatment and prevention of the tumors caused by HPV, thereby completing the present invention.